Hannover Medical School, Department of Neurology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Expert Opin Biol Ther. 2011 Mar;11(3):343-57. doi: 10.1517/14712598.2011.552884. Epub 2011 Jan 25.
Alzheimer's disease (AD) is a progressive, age-dependent, neurodegenerative disorder being the most common cause of dementia. The pathological hallmarks are extracellular amyloid-beta (Aβ) deposition and intracellular neurofibrillary tangles containing hyperphosphorylated tau. Stunning results in vaccination trials in transgenic animals led to an antibody-based approach to develop immunotherapeutics for AD. Thus, several monoclonal antibodies raised against Aβ as well as polyclonal antibodies are currently in clinical testing and some of them already entered Phase III clinical trials. New upcoming experimental approaches like antibodies recognizing specific conformational epitopes, single-chain variable fragment antibodies, or intrabodies give hope of further drug development for this incurable disease.
The rationale and putative mode of action of antibody-based immunotherapy in AD and delineates correlations for other neurodegenerative diseases. Current clinical trials and recent results of therapeutic antibodies in AD are presented.
Antibodies against Aβ will not only broaden the therapeutic repertoire but also our knowledge about the pathology in AD. Further results of the clinical trials and new antibody-based approaches will shed light on the importance of Aβ and its removal in AD.
阿尔茨海默病（AD）是一种进行性、年龄相关性神经退行性疾病，是痴呆的最常见原因。其病理学特征是细胞外淀粉样蛋白-β（Aβ）沉积和含有过度磷酸化 tau 的细胞内神经原纤维缠结。在转基因动物的疫苗试验中令人惊叹的结果促使人们采用基于抗体的方法来开发针对 AD 的免疫疗法。因此，目前有几种针对 Aβ的单克隆抗体和多克隆抗体正在进行临床试验，其中一些已经进入 III 期临床试验。新出现的实验方法，如识别特定构象表位的抗体、单链可变片段抗体或内抗体，为这种无法治愈的疾病的进一步药物开发带来了希望。
AD 中基于抗体的免疫疗法的基本原理和推测作用模式，并阐述了其与其他神经退行性疾病的相关性。介绍了目前正在进行的临床试验和 AD 治疗性抗体的最新结果。
针对 Aβ的抗体不仅将拓宽治疗方案，还将加深我们对 AD 病理学的认识。临床试验的进一步结果和新的基于抗体的方法将阐明 Aβ及其在 AD 中清除的重要性。
